OPD5 / Oncopeptides - LARVOL DELTA

Alkylating Peptide-Drug Conjugates in Glioblastoma - Towards Translational Assessment (EANO 2026) - "Standard care (surgery followed by temozolomide with radiotherapy) provides modest benefit and is less effective in tumors with high MGMT expression. These studies show that intravenous melflufen and OPD5 can penetrate the BBB and achieve intratumoral enrichment. The apparent MGMT‑independent activity suggests potential to address an important resistance mechanism. A window‑of‑opportunity study will test translational relevance by linking human exposure (PK) to early tissue responses (PD)."

Brain Cancer • Glioblastoma • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • MGMT

Mitochondrial DNA Damage Contributes to the Cytotoxic Effect of Lipophilic Alkylating Peptide-Drug Conjugates (EANO 2026) - "Screening drug response in GB cell cultures, representing all subtypes, and in ex vivo patient tissue, alkylkating PDCs show superior response compared to other alkylators, including temozolomide...Material and PDCs, including melflufen and OPD5, and their metabolites were analyzed for cellular and mitochondrial localization in cancer cells and isolated mitochondria...PDCs induced similar damage to both nuclear and mitochondrial DNA, a feature not observed with other compounds utilizing the same cytotoxic payload (melphalan and cyclophosphamide)... Alkylating PDCs target mitochondria and induce mitochondrial DNA damage that contributes to its cytotoxic mechanism. Dual targeting of nuclear and mitochondrial DNA is a plausible explanation for the observation that alkylating PDCs overcome resistance mediated by cell cycle regulation and DNA repair pathways. This could be of special importance in GB since GB cells are more reliant on mitochondria for its energy production,..."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Next‑Generation Alkylating Peptide-Drug Conjugates overcome major resistance mechanisms and prolong survival in MGMT unmethylated Glioblastoma PDOX model (EANO 2026) - " Alkylating PDC, including our lead candidate OPD5, showed superior in vitro cytotoxicity versus conventional alkylators (temozolomide, lomustine) and alkylators in clinical development in over 25 GB cell cultures representing all GB subtypes. The preclinical data demonstrates that PDCs can overcome major resistance mechanisms in GB, including unmethylated MGMT, and achieve effective BBB penetration. The cytotoxicity of our alkylating PDCs were superior in vitro and ex vivo to both conventional alkylators and novel alkylators in clinical trials. The significant survival benefit observed in unmethylated MGMT PDOX models supports further clinical development of PDCs as a promising therapeutic strategy for newly diagnosed and recurrent GB, including treatment resistant disease.This research was partly sponsored by a Eurostars 3 grant, # 2328."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

U.S. Food and Drug Administration removes clinical hold of Oncopeptides’ pipeline drug OPD5 (Oncopeptides Press Release) - "Oncopeptides AB...announces the U.S. Food and Drug Administration (FDA) has lifted the clinical hold previously placed on Oncopeptides’ next-gen drug OPD5. Based on the company’s proprietary Peptide Drug Conjugate (PDC) platform, OPD5 is a follow-on molecule to Oncopeptides’ flagship drug melflufen (branded in Europe as Pepaxti) with a potentially improved risk/benefit profile and enhanced intellectual property protection. OPD5 would initially target multiple myeloma and could potentially be expanded with other indications and diseases over time....As a next step, Oncopeptides will continue to prepare for a new clinical study, OP-502, to assess the safety, tolerability and efficacy of OPD5."

FDA event • Multiple Myeloma

COAST: A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: Oncopeptides AB; N=42 ➔ 0; Suspended ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

COAST: A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=42; Suspended; Sponsor: Oncopeptides AB; Recruiting ➔ Suspended

Clinical • Trial suspension • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

COAST: A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Oncopeptides AB

Clinical • New P1 trial • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

[VIRTUAL] COAST (OP-501): FIRST IN MAN PHASE I MULTICENTER STUDY EVALUATING OPD5 AS A MYELOABLATIVE CONDITIONING REGIMEN IN RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM) (EBMT 2021) - " As OPD5 has similar preclinical pharmacokinetic and lipophilic properties as melflufen, it is of significant medical interest to investigate the benefit-risk profile of OPD5 as a conditioning regimen in patients where salvage ASCT is not currently considered standard of care. Findings from this first-in-man study will potentially demonstrate the value of OPD5 as a myeloablative therapy followed by stem cell support, justifying further clinical development."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Mucositis • Multiple Myeloma • Oncology • Transplantation

[VIRTUAL] COAST (OP-501): FIRST IN MAN PHASE I MULTICENTER STUDY EVALUATING OPD5 AS A MYELOABLATIVE CONDITIONING REGIMEN IN RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM) (EBMT 2021) - " As OPD5 has similar preclinical pharmacokinetic and lipophilic properties as melflufen, it is of significant medical interest to investigate the benefit-risk profile of OPD5 as a conditioning regimen in patients where salvage ASCT is not currently considered standard of care. Findings from this first-in-man study will potentially demonstrate the value of OPD5 as a myeloablative therapy followed by stem cell support, justifying further clinical development."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Mucositis • Multiple Myeloma • Oncology • Transplantation

[VIRTUAL] COAST (OP-501): FIRST IN MAN PHASE I MULTICENTER STUDY EVALUATING OPD5 AS A MYELOABLATIVE CONDITIONING REGIMEN IN RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM) (EBMT 2021) - " As OPD5 has similar preclinical pharmacokinetic and lipophilic properties as melflufen, it is of significant medical interest to investigate the benefit-risk profile of OPD5 as a conditioning regimen in patients where salvage ASCT is not currently considered standard of care. Findings from this first-in-man study will potentially demonstrate the value of OPD5 as a myeloablative therapy followed by stem cell support, justifying further clinical development."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Mucositis • Multiple Myeloma • Oncology • Transplantation

[VIRTUAL] COAST (OP-501): FIRST IN MAN PHASE I MULTICENTER STUDY EVALUATING OPD5 AS A MYELOABLATIVE CONDITIONING REGIMEN IN RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM) (EBMT 2021) - " As OPD5 has similar preclinical pharmacokinetic and lipophilic properties as melflufen, it is of significant medical interest to investigate the benefit-risk profile of OPD5 as a conditioning regimen in patients where salvage ASCT is not currently considered standard of care. Findings from this first-in-man study will potentially demonstrate the value of OPD5 as a myeloablative therapy followed by stem cell support, justifying further clinical development."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Mucositis • Multiple Myeloma • Oncology • Transplantation

Oncopeptides: INTERIM REPORT Q3 2020 (PRNewswire) - "Patient enrolment for the phase 1/2 study in AL-amyloidosis began, this is the first study with melflufen in an indication outside multiple myeloma. The phase 2 PORT study evaluating alternative administration of melflufen and dexamethasone in multiple myeloma started. Oncopeptides entered into a €40 M loan agreement with the European Investment Bank (EIB). An IND application was submitted to the FDA to initiate clinical studies with OPD5, Oncopeptides' second drug candidate."

Enrollment open • Financing • IND • Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology